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Bipolar Disorders 2013 Ronald A. Remick, MD, FRCP(C) Medical Director, Mood Disorder Association of British Columbia Email : [email protected] Sophia I. Zisman, Bsc Hons. St. George’s University of London Epidemiology ① Lifetime prevalence : • • ② ③ bipolar I : 0.8% bipolar II : 0.6% (Murphy, 2000) Bipolar disorder is the 6th leading cause of disability, in people aged between 15-44, worldwide (depression is 2nd!) At any given point in time, 60% of patients with bipolar disorder are not in treatment Mood Disorders and the Workplace Work related economic losses due to depression are estimated to cost 6 billion dollars per year in Canada Health Report, Statistics Canada, 2006 Mood Disorders and the Workplace Absenteeism vs. Presenteeism • • Presenteeism (lost productivity while at work) – likely a more significant problem with mood disorders than previously recognized in Canada Productivity loss from presenteeism due to depression is 4 hours/week while loss from absenteeism is but 1 hour/week (between $6-60 billion loss per annum)! Epidemiology ① ② ③ The course of bipolar I is 9-10 cycles during a lifetime – often stabilizing after 4-5 cycles Without treatment the average depressive episode is 10 weeks and average manic episode is 5 weeks 60% of patients have an increase in episode intensity/duration with age What about the role of ‘stress’ in bipolar illness? Disruption in sleep, but not ‘stress’ can lead to a bipolar relapse. Early childhood ‘trauma’ is NOT causative in bipolar illness, however; ① sexual abuse – may increase risk of suicide attempts ② physical abuse – may increase risk of manic relapses ③ sexual/physical abuse – may lead to earlier illness onset Genetics of Bipolar Illness • • • Polygenic inheritance – fifty percent of bipolar patients have a family history of bipolar illness. Linkage studies (in several studies) have identified markers on chromosome 18 & 22. New research is working to identify individuals at risk which will possibly lead to superior treatments in the future. Evolving genetic concepts ① ② Endophenotypes are gene intermediaries that turn on or turn off a specific gene ‘Stress/adversity can influence endophenotypes. That is, stress or adversity can turn on or turn off certain genes that can either trigger depression (vulnerability) or protect from depression (resiliency) STRESS and the BRAIN CRF ACTH Adrenaline cAMP BDNF Brain Cell Growth STRESS and the BRAIN CRF ACTH Adrenaline cAMP BDNF Brain Cell Growth Hypothalamus CRF STRESS Hippocampal Shrinkage Limbic System Mood dysregulation Memory impairment Pituitary ACTH Adrenal Cortex Apoptosis/neuron death Cortisol + Adrenaline Diagnosing Bipolar Disorders Diagnosis of depression ① ② A distinct mood change (depressed, irritable, anxious, etc) for at least two weeks Four or more SIGECAPS Sleep Interest Guilt Energy Concentration Appetite Psychomotor Activity Suicide Diagnosis of Mania/Hypomania ① ② A distinct mood change (elated, irritable, expansive, etc) for > one week (four days for hypomania) Three or more GST RAID : S leep(decreased) A gitation Rapid thoughts Grandiosity T alkative I mpaired judgement Sleep Agitation D istractible Talkative Impaired judgment Distractible Diagnosing bipolar illness ① ② ③ Distinguish bipolar I (mania) from bipolar II (hypomania) Bipolar II is among the most frequently missed diagnoses in psychiatry The diagnosis of bipolar II disorder is risky, at best, without collateral information. Diagnosis of Hypomania Doctors often fail to ask key questions (of a family member and the patient) that assist in the diagnosis of bipolar II disorder … “ Has there been a period of time when you were feeling so good or hyper that other people thought you were not your normal self, or were so hyper you got into trouble?” “ What about a period of time when you were so irritable that you would shout at people or start fights or arguments?” Treatment of Bipolar Disorders Treatment of Bipolar Disorders Bipolar disorder is a chronic illness: Expect exacerbations and remissions Long term chemotherapy is the rule not the exception It is risky, at best, to treat bipolar patients in a vacuum i.e. without the involvement of family/significant others Treatment of Bipolar Illness 1 Psychological Interventions 2 Biological Interventions Psychological Interventions Psycho education Psychotherapy • Mood Disorders Association of British Columbia http www.mdabc.net • Internet/ readings www.patient.co.uk, www.crestbd.ca • Cognitive behavioural therapy(CBT) for the depressive phase of the illness • CBT to prevent manic relapse Cognitive Behavioral Therapy (CBT) • • • The evidence based psychotherapies are AS EFFECTIVE as antidepressants in mild/moderate MDD. CBT is accessible in British Columbia. CBT response rate(8-12 weekly sessions) = 65%. Cognitive Behavioral Therapy Identify automatic maladaptive thoughts and distorted beliefs that lead to depressive moods Use a systematic approach to reinforce positive coping behaviors Learn strategies to modify these beliefs and practice adaptive thinking patterns Accessibility Private Psychologist Public Resources Online • Not covered by medical insurance • The majority of outpatient psychiatry departments in hospitals offer group based CBT which is covered by MSP funding. Enquire at your local hospital or with your doctor! • www.carmha.ca/publications - ‘antidepressant skills workbook (free download)-an outstanding self directed CBT workbook • www.moodgym.anu.edu.au Biological Treatments for bipolar disorders ① ② ③ ④ ⑤ ⑥ ⑦ LITHIUM VALPROIC ACID CARBAMAZEPINE LAMOTROGINE ATYPICAL ANTIPSYCHOTICS ANTIDEPRESSANTS OTHER ANTICONVULSANTS Lithium Lithium • Expect “two thirds” response to lithium: - 33% complete response - 33% significant mood attenuation - 33% no response/intolerance Complete response No response/intolerance Significant mood attenuation • “anti-suicide” effect of lithium • Lithium remains the ‘GOLD STANDARD’ in treating bipolar illness and is among the most effective and underutilized treatments in all of psychiatry! 80 70 60 50 40 30 20 10 0 Suicide attempts before, during, one year, and two years post lithium treatment Valproic Acid • • • • • Valproic acid (divalproex; Depokoate; Epival) is an effective antimanic agent The evidence for the prophylactic efficacy of valproic is still not clear (one short RCT, pharmaceutical company sponsored) Recommended as first line maintenance therapy (Dr. Remick) Valproic is far superior as an anti manic rather than an antidepressant preventative agent Recommended to be used as a 1st line combination therapy medication for the treatment of acute BD-1 depression Serum levels appropriate (versus no defined therapeutic range with carbamazepine) Carbamazepine • • • • • Carbamazepine (Tegretol) is an effective antimanic agent (19 studies) Carbamazepine is an effective prophylactic agent (10 RCTs), but likely less effective than lithium (Davis et al, 1999) Carbamazepine appears to be a forgotten (yet very effective) treatment in bipolar illness Oxcarbazepine (Trileptil) is being touted as a ‘similar’ but ‘superior’ medication to carbamazepine, but recent studies shed some doubt Recommended as 3rd line therapy in the treatment of depression in bipolar disorder Lamotrogine (Lamictal) ① ② ③ There is increasing evidence that lamotrogine is an effective agent in treating both bipolar I and II depression currently recommended as a first line agent in the treatment of depression. There is very limited (but some) evidence that lamotrogine is an effective anti-manic or prophylactic agent. Lamotrogine has a relatively benign (e.g. non sedative, weight neutral) side effect profile. Dose range not determined but likely 100300mg/day Other anticonvulsants in bipolar disorder There is NO evidence that gabapentin (Neurontin) or topiramate (Topramax) has any benefit at all in the treatment of bipolar depression, bipolar mania, and/or the preventative/prophylactic treatment of bipolar illness. They are not recommended in the treatment of bipolar disorder. Typical/Atypical Antipsychotics ① ② ③ ④ Quetiapine and Olanzepine show evidence of mood stabilizing properties – both antidepressant and antimanic. Current guidelines suggest Quetiapine is preferable to other antipsychotic agents due to its side effect profile. Olanzapine is a 3rd line treatment due to its side effect profile. Side effects can included: weight gain, dyslipidemia, & diabetes with atypicals; especially olanzapine(Zyprexa) and clozapine(Clozaril) but also risperidone(Risperdol) and quetiapine (Seroquel) Lifestyle • The diet of individuals with SMI(Serious Mental Illness) has been characterized as high fat, high in calories and high in simple carbohydrates. • Patients with SMI are less active then those in the general population and are more likely to walk as their sole form of physical activity. • Smoking rates are elevated in the SMI and range between 32% and 92% in schizophrenia samples. “ Do not rashly use every new product of which the peripatetic siren sings. Consider what surprising reactions may occur in the laboratory from the careless mixing of unknown substances. Be as considerate of your patient and yourself as you are of the test tube.” Sir William Osler Bipolar Medications and Pregnancy ① ② ③ Lithium – ensure careful monitoring during pregnancy Valproic Acid – proven to be harmful for fetuses, it is recommended that new mothers switch to another treatment Carbamazepine – should only be used if it is the only option Always contact your physician if you are being treated for bipolar disorder and are planning to fall pregnant. Managing depressive and manic relapses “don’t throw out the baby with the bathwater” If the treatment has muted or attenuated the illness consider adding a second treatment rather than eliminating the treatment that is offering partial efficacy. Managing Depressive Relapse ① ② Don’t throw out the baby with the bathwater! The risk of an antidepressant induced manic switch in both bipolar I/II is < 10% (SSRI’s & bupropion < TCA and SNRI) Managing Depressive Relapse Treatment options: a. second mood stabilizer (I) (lamotrogine) b. antidepressant (II,I)/ lamotrogine c. CBT(I,II) d. ECT(I,II) Managing Manic/Hypomanic Relapse 1. Don’t throw out the baby with the bath water 2. Other treatment options: a. hospital care (I) b. no treatment intervention (II) c. second mood stabilizer (I/II) d. atypical /typical antipsychotic (I/II) e. benzodiazepine (II) f. ECT (I) Prevention of future manic relapses – Ulysses Agreement ① ② Set it up BEFORE manic relapse with doctors, family, employers, etc. Put it in writing – outline the type of treatment e.g. hospitalization, antipsychotic medication, etc. Factors associated with relapse • • • • • • • • medication adherence (70% to 30%) presence of subsyndromal symptoms baseline psychosocial stress higher number of prior episode BD-11 versus BD-I female gender substance abuse Rapid cycling (>4 episodes per year) “Grey zones” in bipolar illness…(topics for future presentations) ① ② ③ ④ ⑤ ⑥ “Stressful life problems” versus mild depressive relapse The role of psychological “adversity” in bipolar illness To treat or not treat hypomania Social/family/vocational stigma “Doctor should we have children?” Bipolar illness and creativity What’s the deal with childhood bipolar illness? ① ② ③ ④ ⑤ The onset in bipolar illness can be in late adolescence, particularly in children of bipolar parents. The diagnosis of childhood bipolar illness (i.e. ages 5-15)is very different in USA compared to Canada, where childhood bipolar illness is virtually nonexistent. In Canada, the onset of bipolar illness typically begins with a lengthy depressive episode. In the USA, children with mood lability/irritability, anxiety and insomnia are often given a diagnosis of childhood bipolar illness. The USA position is not consistent with decades of age of onset research, genetic studies, or current diagnostic criteria for bipolar disorders. “Doctor, should we have children?” • • • • The risks are real, but small (2% versus 15%). Illness severity is not related to the severity of the illness in the family. Illness onset is at least twenty years in the future with extensive new developments and treatments on the way. Bipolar illness, without any other risk factors, in a parent is certainly not an exclusion to having and effectively parenting children. The relationship between creativity and bipolar illness ① ② ③ ④ ⑤ Many studies have shown that between 20 and 35% of artists (musicians, painters, writers, poets, etc ) develop bipolar illness where the rate of bipolar illness in the population is about 2%. The higher rate of bipolar illness cannot be explained by ‘stressful’ life style, poverty, etc. Severe manic and depressive episodes impair creative output. Creativity and bipolar illness have a familial (i.e. genetic) link. Touched with Fire : Manic Depressive Illness and the Artistic Temperment. by Kay Redfield Jamieson (1993)